Does Adding Adjuvant Bevacizumab to Capecitabine Benefit Patients With Colorectal Cancer?
Kerr et al found that adding adjuvant bevacizumab (Avastin) to capecitabine did not improve disease-free survival in unselected patients with stage III or high-risk stage II colorectal cancer. The results of the phase III QUASAR 2 trial were reported in The Lancet Oncology.
Study Details
In the open-label trial, 1,941 evaluable patients from 170 sites in Australia, Austria, Czech Republic, New Zealand, Serbia, Slovenia, and the UK who had undergone potentially curative surgery were randomized between April 2005 and October 2010 to receive eight 3-week cycles of oral capecitabine alone (1,250 mg/m² twice daily for 14 days followed by 7 days off; n = 968) or capecitabine plus 16 cycles of 7.5 mg/kg on day 1 of each cycle (n = 973).
The primary endpoint was 3-year disease-free survival in the intent-to-treat population. Overall, median age was 65 years, 57% were male, 38% to 39% had stage II disease, and the primary site was the colon in 88%.
After accrual of the target population for the primary endpoint, recruitment was closed by the data safety monitoring committee, due to negative results with the addition of bevacizumab to chemotherapy in stage III colorectal cancer in another trial (AVANT) and the perceived potential risk of harm.
Survival Data
Median follow-up was 4.92 years. Disease-free survival at 3 years was 75.4% in the bevacizumab/capecitabine group vs 78.4% in the capecitabine group (hazard ratio [HR] = 1.06, P = .54).
In a subgroup analysis, hazard ratios tended to favor capecitabine alone. Among 1,197 patients with stage III disease, 3-year disease-free survival was 71.3% with bevacizumab/capecitabine vs 74.5% with capecitabine (HR = 1.07, P = .52).
Overall survival at 3 years in the intent-to-treat population was 87.5% with bevacizumab/capecitabine vs 89.4% with capecitabine alone (HR = 1.11, P = .33).
Adverse Events
The most common grade 3 or 4 adverse events were hand-foot syndrome (27% of bevacizumab group vs 21% of capecitabine group) and diarrhea (11% vs 11%). The bevacizumab group had expected increases in any-grade hypertension (33% vs8%), proteinuria (21% vs5%), and wound-healing problems (3% vs2%).
A total of 571 serious adverse events were reported, including 350 in the bevacizumab group and 221 in the capecitabine group; most were gastrointestinal (n = 245) or cardiovascular (n = 169) events. A total of 23 deaths within 6 months of randomization were considered related to treatment, including 15 in the bevacizumab/capecitabine group and 8 in the capecitabine group.
The investigators concluded: “The addition of bevacizumab to capecitabine in the adjuvant setting for colorectal cancer yielded no benefit in the treatment of an unselected population and should not be used.”
The study was funded by Roche.
Rachel S. Kerr, FRCP, of the University of Oxford, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
